Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
Nat Commun. 2014 Dec 11;5:5701. doi: 10.1038/ncomms6701.
Roquin proteins mediate mRNA deadenylation by recognizing a conserved class of stem-loop RNA degradation motifs via their Roquin domain. Here we present the crystal structure of a Roquin domain, revealing a mostly helical protein fold bearing a winged helix-turn-helix motif. By combining structural, biochemical and mutation analyses, we gain insight into the mode of RNA binding. We show that the winged helix-turn-helix motif is involved in the binding of constitutive decay elements-containing stem-loop mRNAs. Moreover, we provide biochemical evidence that Roquin proteins are additionally able to bind to duplex RNA and have the potential to be functional in different oligomeric states.
Roquin 蛋白通过其 Roquin 结构域识别保守的茎环 RNA 降解基序类，从而介导 mRNA 的去腺苷酸化。在此，我们呈现了 Roquin 结构域的晶体结构，揭示了一种主要由螺旋组成的蛋白折叠，带有翼状螺旋-转角-螺旋基序。通过结合结构、生化和突变分析，我们深入了解了 RNA 结合的模式。我们表明，翼状螺旋-转角-螺旋基序参与结合含有组成性降解元件的茎环 mRNA。此外，我们提供了生化证据表明，Roquin 蛋白还能够结合双链 RNA，并有可能在不同的寡聚状态下发挥功能。
